Spectinomycin is a known antibiotic having the formula X. The numbering of carbon atoms for the ring system of spectinomycin; as also used hereinafter for analogs thereof, is as shown. Spectinomycin was first prepared in a microbiological process. See Bergy, et al., U.S. Pat. No. 3,234,092.
Presently, many analogs of spectinomycin are known which exhibit desirable biological activity. Further, several chemical processes and intermediates are known for the preparation of spectinomycin and its various analogs. Those which are believed to be the closest to the present process and novel intermediates therein are summarized in the following two paragraphs.
Preparation of an enamine having formula I wherein R.sub.1 and R.sub.2 are the same and are blocking groups, and R.sub.3 is acyl which is used as a starting material in the present invention is described in U.S. application Ser. No. 449,304 filed Dec. 13, 1982, now U.S. Pat. No. 4,532,336 which is a Continuation-in-part of U.S. application Ser. No. 359,723 filed Mar. 19, 1982, now abandoned. The preparation is also disclosed in U.S. Pat. No. 4,380,651 filed July 20, 1981, U.S. Pat. No. 4,380,652 filed July 20, 1981, and U.S. Pat. No. 4,420,623 filed Mar. 17, 1982. Enoneacylates used to prepare the enamines (I) are described in U.S. Pat. No. 4,351,771. Therefore, U.S. Pat. Nos. 4,380,651, 4,380,652, 4,420,623 and 4,351,771 are incorporated by reference.
Further, U.S. application Ser. No. 449,304 discloses a process by which a dienone is converted to a large variety of 6'-alkylspectinomycin analogs of similar scope as now disclosed for the 6'-ethylspectinomycin and analogs thereof prepared by the present invention process. The process of U.S. application Ser. No. 449,304 is a copper catalyzed Grignard addition.
The present invention provides an improved Grignard process having novel intermediates. The novel intermediates are dienones having formula II wherein R.sub.1 and R.sub.2 are as described above; and R' is alkyl of from 1-18 carbon atoms, inclusive, which are not disclosed and are not obvious from those previously disclosed in the Grignard process of U.S. Ser. No. 449,304. Further, no low temperature reactions are required in the present process which, furthermore, provides improved yields.